Comparative efficacy and safety of alternative glucocorticoids regimens in patients with ANCA-associated vasculitis: a systematic review.

OBJECTIVE: To compare the efficacy and safety of alternative glucocorticoids (GCs) regimens as induction therapy for patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. DESIGN: Systematic review of randomised controlled trials (RCTs). DATA SOURCES: Medline, Embase, Clinicaltrials.gov and Cochrane Central Register of Controlled Trials up to 10 April 2020. STUDY SELECTION AND REVIEW METHODS: RCTs comparing two (or more) different dose regimens of GC in ANCA-associated vasculitis during induction of remission, regardless of other therapies. Pairs of reviewers independently screened records, extracted data and assessed risk of bias. Two reviewers rated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of 3912 records identified, the full texts of two records met the eligibility criteria. Due to the heterogeneity of population and dose regimen of GCs between the two trials, we descriptively presented the two trials and did not combine the results using meta-analysis. Compared with the standard-dose regimen, the reduced-dose regimen of GC may reduce death risk difference (RD): from -1.7% to -2.1%, low certainty), while not increasing end-stage kidney disease (ESKD) (RD: from -1.5% to 0.4%, moderate certainty). The reduced-dose regimen probably has an important reduction in serious infections at 1 year (RD: from -12.8% to -5.9%, moderate certainty). Reduced-dose regimen of GCs probably has trivial or no effect in disease remission, relapse or health-related quality of life (moderate to high certainty). CONCLUSIONS: The reduced-dose regimen of GC may reduce death at the follow-up of 6 months to longer than 1 year and serious infections while not increasing ESKD. PROSPERO REGISTRATION NUMBER: CRD42020179087

The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>The increasing use of highly active antiretroviral therapy (HAART) and pneumococcal immunization along with shifting community exposures may have altered the burden of <it>Streptococcus pneumoniae </it>disease in HIV-infected persons. We describe the burden and risk factors for pneumococcal disease in the modern era of HIV care and evaluate the use of a 23-valent pneumococcal polysaccharide vaccine (PPV-23).</p> <p>Methods</p> <p>The incidence of invasive pneumococcal disease (IPD) between January 1^st, 2000 and January 1^st, 2010 in a regional HIV population in Southern Alberta, Canada was determined by linking comprehensive laboratory and hospital surveillance data. Clinical and epidemiologic data including risk factors for <it>S. pneumoniae</it>, history of pneumococcal immunization, serotypes of infections, and length of any hospitalizations for pneumococcal disease were evaluated with multivariate analysis. CD4 count and viral load at immunization were evaluated with a nested case-control analysis.</p> <p>Results</p> <p>In 1946 HIV-patients with 11,099 person-years of follow up, there were 68 distinct episodes of pneumococcal disease occurring in 50 patients. Increased risk was seen if female, age >60, Aboriginal ethnicity, lower education, injection drug use, smoking, nadir CD4 <200/μL, chronic obstructive pulmonary disease, and hepatitis C. Overall, the incidence of IPD was 342/100,000 person-years and was reduced to 187/100,000 within three years of PPV-23 immunization (P < 0.01). Although 78% of patients received PPV-23, 74% of IPD episodes were caused by PPV-23 serotypes. In a case-control analysis, HIV viral load at immunization was significantly predictive of PPV-23 failure, while CD4 count was not. 80% of IPD cases required hospitalization: median length of stay was 7 days (range: 1-71); four patients died.</p> <p>Conclusions</p> <p>Despite universal access to intensive measures to prevent pneumococcal disease including the widespread use of HAART and PPV-23 immunization, the incidence of IPD remains high in HIV patients with its associated morbidity and mortality.</p

Activity-Based Funding of Hospitals and Its Impact on Mortality, Readmission, Discharge Destination, Severity of Illness, and Volume of Care: A Systematic Review and Meta-Analysis

Background: Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care. &nbsp; &nbsp; Methods: We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication. &nbsp; &nbsp; Results: Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk = 1.24, 95% CI 1.18–1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences. &nbsp; &nbsp; Conclusions: Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes

A living WHO guideline on drugs for covid-19

CITATION: Agarwal, A. et al. 2022. A living WHO guideline on drugs for covid-19. British Medical Journal, 370. doi:10.1136/bmj.m3379The original publication is available at https://jcp.bmj.com/This living guideline by Arnav Agarwal and colleagues (BMJ 2020;370:m3379, doi:10.1136/bmj.m3379) was last updated on 22 April 2022, but the infographic contained two dosing errors: the dose of ritonavir with renal failure should have read 100 mg, not 50 mg; and the suggested regimen for remdesivir should have been 3 days, not 5-10 days. The infographic has now been corrected.Publishers versio

Increasing HIV Subtype Diversity and Its Clinical Implications in a Sentinel North American Population

BACKGROUND: HIV-1 is a highly diverse virus; subtypes may exhibit differences in rates of transmission, disease progression, neurotoxicity, antiretroviral treatment failure profiles and accuracy of viral load measurements. To date, the HIV epidemic in Canada and the rest of the developed world has been largely due to subtype B; however, shifts in subtype epidemiology could have significant implications.OBJECTIVE: To determine whether there has been an increase in HIV subtype diversity in southern Alberta, Canada.METHODS: All 2358 patients receiving any HIV care between December 31, 2001 and December 31, 2010 were included in a retrospective analysis of subtype prevalence and incidence. In an indexed analysis, subtype trends from 1994 to 2010 were also evaluated.RESULTS: Between 2001 and 2010, the prevalence of non-B HIV subtypes in patients with a known subtype increased from 7% to 24%. In 2010, the most prevalent non-B subtypes were C (65%), A (11%), CRF02_AG (9.7%), CRF01_AE (4.9%), D (3.9%), G (2.9%) and CRF06_cpx (1.5%). In the indexed analysis, there was an overall proportional increase in non-B subtypes of 2.3% per year. The year-over-year increase in the prevalence of patients infected with a nonsubtype B virus increased from 13% from 1995 to 2002 to 27% from 2003 to 2010 (P=0.01). Incident non-B subtype cases increased from 9.6% to 32.4% over these time periods.CONCLUSIONS: This recent and dramatic shift in HIV strain diversity in Canada is unprecedented and may have important public health, research and clinical consequences.Peer Reviewe

A living WHO guideline on drugs for covid-19

Clinical question: What is the role of drugs in the treatment of patients with covid-19?New recommendation: Pre-prints of four randomised trials (from a larger adaptive randomised master protocol) among patients with non-severe illness, and the RECOVERY trial among severe and critically ill patients, triggered this guideline update. This resulted in a conditional recommendation to use a combination of casirivimab and imdevimab in non-severe patients for those at highest risk of severe disease. The RECOVERY trial included a crucial subgroup analysis demonstrating differential benefits (effect modification) associated with serological status. The Guideline Development Group (GDG) made a second conditional recommendation to use casirivmab-imdevimab in patients with severe and critical infection, if the individual has seronegative status.Prior recommendations: (a) A strong recommendation for interleukin-6 receptor blockers (tocilizumab or sarilumab) in patients with severe or critical covid-19; (b) a recommendation not to use ivermectin in patients with covid-19, regardless of disease severity, except in the context of a clinical trial; (c) a strong recommendation against the use of hydroxychloroquine in patients with covid-19, regardless of disease severity; (d) a strong recommendation against the use of lopinavir-ritonavir in patients with covid-19, regardless of disease severity; (e) a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19; (f) a conditional recommendation against systemic corticosteroids in patients with non-severe covid-19; and (g) a conditional recommendation against remdesivir in hospitalised patients with covid-19.How this guideline was created: This living guideline, from the World Health Organization (WHO), provides up to date covid-19 guidance to inform policy and practice worldwide. MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network meta-analysis informed the recommendations. A GDG of content experts, clinicians, patients, ethicists, and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Understanding the new recommendation: In patients with non-severe illness, pooled data showed casirivimab-imdevimab had trivial or no effects on mortality or need for mechanical ventilation, due to very low baseline risk. Evidence demonstrated a likely reduction in need for hospitalisation; the absolute benefit will be greater in those at highest risk of hospitalisation. When moving from evidence to the conditional recommendation to use casirivimab-imdevimab in those at highest risk, the GDG recognised the limited availability, in relation to the large number of patients with non-severe disease, of the medicine and the very small benefits in reducing hospitalisation for low risk patients. Although there is no established decision tool to identify those at highest risk of hospitalisation, factors that substantially increase risk include no prior vaccination, older age, immunosuppression, and the presence of chronic conditions. In patients with severe or critical illness the conditional recommendation reflects the likelihood that any benefits are restricted to patients who are seronegative. A credible subgroup effect demonstrated that, in patients who are seronegative (that is, absence of their own anti-SARS-CoV-2 spike protein antibodies despite active infection), casirivimab-imdevimab probably reduces mortality and may reduce the need for mechanical ventilation. Rapid identification of serological status at the time of presentation of severe or critical illness is necessary. Several rapid, relatively inexpensive tests with adequate performance characteristics are available.Updates: This is a living guideline. It replaces earlier versions (4 September, 20 November, 17 December 2020, 31 March 2021, and 6 July 2021) and supersedes the BMJ Rapid Recommendations on remdesivir published on 2 July 2020. The previous versions can be found as data supplements. New recommendations will be published as updates to this guideline.Readers\u27 note: This is the sixth version (update 5) of the living guideline (BMJ 2020;370:m3379). When citing this article, please consider adding the update number and date of access for clarity

Corticosteroids for sore throat: a clinical practice guideline

status: publishe